Atrasentan in Patients With IgA Nephropathy (ALIGN)

Chinook Therapeutics

Status and phase: Active, not recruiting; Phase 3

Conditions: Immunoglobulin A Nephropathy; IgA Nephropathy

Treatments: Drug: Placebo; Drug: Atrasentan

Study type: Interventional

Funder types: Industry

Identifiers

NCT04573478

CHK01-01

Details and patient eligibility

About

The ALIGN Study is a phase 3, double-blind, placebo-controlled study to compare the efficacy and safety of atrasentan to placebo in patients with IgA nephropathy (IgAN) at risk of progressive loss of renal function.

Full description

Approximately 320 patients with biopsy-proven IgAN will be randomized to receive 0.75 mg atrasentan or placebo daily for 132 weeks. Subjects receive a maximally tolerated and stable dose of a RAS (renin-angiotensin system) inhibitor [such as angiotensin converting enzyme inhibitor (ACEi) or angiotensin-receptor antagonist (ARB)] as part of standard of care. An exception will be made for subjects who are unable to tolerate RAS inhibitor therapy.

Additional subjects receiving a stable dose of SGLT2i will be enrolled to the study. Enrollment in this SGLT2i stable stratum will be in accordance with local regulations in regions that prescribe SGLT2i and will be independent of the 320 subjects enrolled for the primary and secondary analyses.

The primary objective of the study is to evaluate the effect of atrasentan versus placebo on proteinuria as measured by UPCR. Secondary and tertiary objectives include evaluating the change in kidney function over time as measured by eGFR, safety and tolerability, as well as quality of life.

Subjects will have assessments of safety and efficacy over 2 ½ years. To facilitate study participation over this time period, where allowed by local regulations, options for remote study visits using telemedicine and home health may be offered.

Subjects who complete treatment through Week 132 and complete the double-blinded portion of the study may be eligible to enroll in the open label extension of the study to receive atrasentan 0.75 mg daily for up to 48 weeks.

Enrollment: 404 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Double-Blind period:

• Biopsy-proven IgA nephropathy.
• Receiving a maximally tolerated dose of RAS inhibitor therapy (ACEi or ARB) that has been stable for at least 12 weeks. Exceptions from this requirement will be made for subjects who are unable to tolerate RAS inhibitor therapy.
• Total urine protein ≥1 g/day as measured via 24-hour urine collection by central laboratory at Screening.
• eGFR of at least 30 mL/min/1.73 m^2 at Screening based on the CKD-EPI equation.
• Willing and able to provide informed consent and comply with all study requirements.
• SGLT2i Stable Stratum Only - Receiving a stable dose of an SGLT2i (per Investigator choice) in addition to a maximally tolerated and optimized dose of a RAS inhibitor that has been stable for at least 12 weeks prior to Screening.
• All fertile men and WOCBP who engage in heterosexual intercourse must be willing to abide with highly effective forms of contraception, as specified in the protocol, throughout the study and for 1 month afterward. In WOCBP, use of contraceptive agents must have been started at least 1 month prior to Baseline.

Open-Label Period:

• Willing and able to provide informed consent and comply with all OL extension study visits and study procedures.
• Completed treatment through Week 132 and completed the Week 136 visit.
• All fertile men and WOCBP who engage in heterosexual intercourse must be willing to abide with highly effective forms of contraception, as specified in the protocol, throughout the study and for 1 month afterward. In WOCBP, use of contraceptive agents must have been continued after completing the double-blind portion of the study.

Exclusion criteria

Double-blind period:

• Concurrent diagnosis of another cause of chronic kidney disease including diabetic kidney disease or another primary glomerulopathy.
• Clinical diagnosis of nephrotic syndrome.
• BNP value of > 200 pg/mL at Screening.
• Platelet count <80,000 per μL at Screening.
• History of organ transplantation (subjects with history of corneal transplant are not excluded).
• Use of systemic immunosuppressant medications.
• Hemoglobin below 9 g/dL at Screening or prior history of blood transfusion for anemia within 3 months of Screening.

Open-label period:

• eGFR < 25 mL/min/1.73m^2 or evidence of rapidly decreasing eGFR, including unrecovered acute kidney injury or expected to require renal replacement therapy within 3 months
• BNP value of > 200 pg/mL at OL Screening.
• Platelet count < 80,000 per μL at OL Screening.
• Hemoglobin below 9 g/dL at OL screening or prior history of blood transfusion for anemia within 3 months of OL Screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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404 participants in 2 patient groups, including a placebo group

Atrasentan

Experimental group

Description:

Double-blind Period: Once daily oral administration of 0.75 mg atrasentan for 132 weeks. Open-label Extension Period: Once daily oral administration of 0.75 mg atrasentan for 48 weeks after completion of 132 weeks on atrasentan or placebo.

Treatment:

Drug: Atrasentan

Placebo

Placebo Comparator group

Description:

Double-blind Period: Once daily oral administration of placebo for 132 weeks

Treatment:

Drug: Placebo